Trans-activation response element

Last updated
Trans-activation response element (TAR)
RF00250.jpg
Identifiers
Symbolmir-TAR
Alt. SymbolsTAR
Rfam RF00250
Other data
RNA type Gene; miRNA
Domain(s) Viruses
GO GO:0035068 GO:0035195
SO SO:0000233 SO:0001244
PDB structures PDBe

The HIV trans-activation response (TAR) element is an RNA element which is known to be required for the trans-activation of the viral promoter and for virus replication. The TAR hairpin is a dynamic structure [1] that acts as a binding site for the Tat protein, and this interaction stimulates the activity of the long terminal repeat promoter. [2]

Further analysis has shown that TAR is a pre-microRNA that produces mature microRNAs from both strands of the TAR stem-loop. [3] These miRNAs are thought to prevent infected cells from undergoing apoptosis by downregulating the genes ERCC1, IER3, [4] CDK9, and Bim. [5]

Human polyomavirus 2 (JC virus) contains a TAR-homologous sequence in its late promoter [6] that is responsive to HIV-1 derived Tat. [7] [8]

Related Research Articles

The genome and proteins of HIV (human immunodeficiency virus) have been the subject of extensive research since the discovery of the virus in 1983. "In the search for the causative agent, it was initially believed that the virus was a form of the Human T-cell leukemia virus (HTLV), which was known at the time to affect the human immune system and cause certain leukemias. However, researchers at the Pasteur Institute in Paris isolated a previously unknown and genetically distinct retrovirus in patients with AIDS which was later named HIV." Each virion comprises a viral envelope and associated matrix enclosing a capsid, which itself encloses two copies of the single-stranded RNA genome and several enzymes. The discovery of the virus itself occurred two years following the report of the first major cases of AIDS-associated illnesses.

<span class="mw-page-title-main">Long terminal repeat</span> DNA sequence

A long terminal repeat (LTR) is a pair of identical sequences of DNA, several hundred base pairs long, which occur in eukaryotic genomes on either end of a series of genes or pseudogenes that form a retrotransposon or an endogenous retrovirus or a retroviral provirus. All retroviral genomes are flanked by LTRs, while there are some retrotransposons without LTRs. Typically, an element flanked by a pair of LTRs will encode a reverse transcriptase and an integrase, allowing the element to be copied and inserted at a different location of the genome. Copies of such an LTR-flanked element can often be found hundreds or thousands of times in a genome. LTR retrotransposons comprise about 8% of the human genome.

<span class="mw-page-title-main">Retroviral psi packaging element</span>

The retroviral psi packaging element, also known as the Ψ RNA packaging signal, is a cis-acting RNA element identified in the genomes of the retroviruses Human immunodeficiency virus (HIV) and Simian immunodeficiency virus (SIV). It is involved in regulating the essential process of packaging the retroviral RNA genome into the viral capsid during replication. The final virion contains a dimer of two identical unspliced copies of the viral genome.

<span class="mw-page-title-main">Cyclin-dependent kinase 9</span> Protein-coding gene in the species Homo sapiens

Cyclin-dependent kinase 9 or CDK9 is a cyclin-dependent kinase associated with P-TEFb.

<span class="mw-page-title-main">Cyclin T1</span> Protein-coding gene in humans

Cyclin-T1 is a protein that in humans is encoded by the CCNT1 gene.

<span class="mw-page-title-main">POLR2B</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB2 is an enzyme that in humans is encoded by the POLR2B gene.

<span class="mw-page-title-main">RELB</span> Protein-coding gene in the species Homo sapiens

Transcription factor RelB is a protein that in humans is encoded by the RELB gene.

<span class="mw-page-title-main">POLR2L</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerases I, II, and III subunit RPABC5 is a protein that in humans is encoded by the POLR2L gene.

<span class="mw-page-title-main">POLR2J</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB11-a is an enzyme that in humans is encoded by the POLR2J gene.

<span class="mw-page-title-main">POLR2K</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerases I, II, and III subunit RPABC4 is a protein that in humans is encoded by the POLR2K gene.

<span class="mw-page-title-main">RNA polymerase II subunit B4</span> Protein-coding gene in the species Homo sapiens

DNA-directed RNA polymerase II subunit RPB4 is an enzyme that in humans is encoded by the POLR2D gene.

<span class="mw-page-title-main">PURA</span> Protein-coding gene in the species Homo sapiens

Pur-alpha is a protein that in humans is encoded by the PURA gene located at chromosome 5, band q31.

<span class="mw-page-title-main">TAF7</span> Protein-coding gene in the species Homo sapiens

Transcription initiation factor TFIID subunit 7 also known as TAFII55 is a protein that in humans is encoded by the TAF7 gene.

<span class="mw-page-title-main">HTATSF1</span> Protein-coding gene in the species Homo sapiens

HIV Tat-specific factor 1 is a protein that in humans is encoded by the HTATSF1 gene.

<span class="mw-page-title-main">TARBP2</span> Protein

RISC-loading complex subunit TARBP2 is a protein that in humans is encoded by the TARBP2 gene.

<span class="mw-page-title-main">TARBP1</span> Protein-coding gene in the species Homo sapiens

Probable methyltransferase TARBP1 is an enzyme that in humans is encoded by the TARBP1 gene.

Tat (HIV)

In molecular biology, Tat is a protein that is encoded for by the tat gene in HIV-1. Tat is a regulatory protein that drastically enhances the efficiency of viral transcription. Tat stands for "Trans-Activator of Transcription". The protein consists of between 86 and 101 amino acids depending on the subtype. Tat vastly increases the level of transcription of the HIV dsDNA. Before Tat is present, a small number of RNA transcripts will be made, which allow the Tat protein to be produced. Tat then binds to cellular factors and mediates their phosphorylation, resulting in increased transcription of all HIV genes, providing a positive feedback cycle. This in turn allows HIV to have an explosive response once a threshold amount of Tat is produced, a useful tool for defeating the body's response.

<span class="mw-page-title-main">Rev (HIV)</span> HIV-1 regulating protein

Rev is a transactivating protein that is essential to the regulation of HIV-1 protein expression. A nuclear localization signal is encoded in the rev gene, which allows the Rev protein to be localized to the nucleus, where it is involved in the export of unspliced and incompletely spliced mRNAs. In the absence of Rev, mRNAs of the HIV-1 late (structural) genes are retained in the nucleus, preventing their translation.

<span class="mw-page-title-main">Kissing stem-loop</span>

In genetics, a kissing stem-loop, or kissing stem loop interaction, is formed in ribonucleic acid (RNA) when two bases between two hairpin loops pair. These intra- and intermolecular kissing interactions are important in forming the tertiary or quaternary structure of many RNAs.

Human Immunodeficiency Virus (HIV) has the capability to enter a latent stage of infection where it exists as a dormant provirus in CD4+ T-cells. Most latently infected cells are resting memory T cells, however a small fraction of latently infected cells isolated from HIV patients are naive CD4 T cells.

References

  1. Lu, Jia; Kadakkuzha, Beena M.; Zhao, Liang; et al. (2011). "Dynamic Ensemble View of the Conformational Landscape of HIV-1 TAR RNA and Allosteric Recognition". Biochemistry. 50 (22): 5042–5057. doi:10.1021/bi200495d. PMID   21553929.
  2. Kulinski, T; Olejniczak M; Huthoff H; Bielecki L; Pachulska-Wieczorek K; Das AT; Berkhout B; Adamiak RW (2003). "The apical loop of the HIV-1 TAR RNA hairpin is stabilized by a cross-loop base pair". J Biol Chem. 278 (40): 38892–38901. doi: 10.1074/jbc.M301939200 . PMID   12882959.
  3. Ouellet DL, Plante I, Landry P, et al. (April 2008). "Identification of functional microRNAs released through asymmetrical processing of HIV-1 TAR element". Nucleic Acids Res. 36 (7): 2353–2365. doi:10.1093/nar/gkn076. PMC   2367715 . PMID   18299284.
  4. Klase Z, Winograd R, Davis J, et al. (2009). "HIV-1 TAR miRNA protects against apoptosis by altering cellular gene expression". Retrovirology. 6: 18. doi: 10.1186/1742-4690-6-18 . PMC   2654423 . PMID   19220914.
  5. Narayanan, A; Iordanskiy, S; Das, R; Van Duyne, R; Santos, S; Jaworski, E; Guendel, I; Sampey, G; Dalby, E; Iglesias-Ussel, M; Popratiloff, A; Hakami, R; Kehn-Hall, K; Young, M; Subra, C; Gilbert, C; Bailey, C; Romerio, F; Kashanchi, F (5 July 2013). "Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA". The Journal of Biological Chemistry. 288 (27): 20014–20033. doi: 10.1074/jbc.m112.438895 . PMC   3707700 . PMID   23661700.
  6. Chowdhury, Mashiul; Taylor, J. Paul; Chang, Chun-Fan; Rappaport, Jay; Khalili, Kamel (1992). "Evidence that a Sequence Similar to TAR Is Important for Induction of the JC Virus Late Promoter by Human Immunodeficiency Virus Type 1 Tat". Journal of Virology. 66 (12): 7355–7361. doi: 10.1128/jvi.66.12.7355-7361.1992 . PMC   240440 . PMID   1331525.
  7. Nukuzuma, Souichi; Kameoka, Masanori; Sugiura, Shigeki; Nakamichi, Kazuo; Nukuzuma, Chiyoko; Miyoshi, Isao; Takegami, Tsutomu (2012). "Exogenous human immunodeficiency virus-1 protein, Tat, enhances replication of JC virus efficiently in neuroblastoma cell lines". Journal of Medical Virology. 84 (4): 555–561. doi:10.1002/jmv.23239. PMID   22337293. S2CID   35625307.
  8. Krachmarov, Chavdar P.; Chepenik, Lara G.; Barr-Vagell, Sharon; Khalili, Kamel; Johnson, Edward M. (1996). "Activation of the JC virus Tat-responsive transcriptional control element by association of the Tat protein of human immunodeficiency virus 1 with cellular protein Purα". Proceedings of the National Academy of Sciences of the United States of America. 93 (24): 14112–14117. Bibcode:1996PNAS...9314112K. doi: 10.1073/pnas.93.24.14112 . PMC   34556 . PMID   8943069.